Focus

We are interested in the how individual members of the gut microbiota influence the host immune system, how they promote colonization resistance and how they interact with the host during health and disease.

Introduction

The gut microbiota plays an integral part in shaping the host immune system and amongst its many functions, helps to protect the host from pathogens. How individual bacterial species contribute to colonization resistance is still poorly understood. For now, the foremost commensal associated with colonization resistance in the gut, as well as at distal mucosal sites, is the Clostridium-related commensal segmented filamentous bacteria (SFB). SFB is a common commensal in many vertebrates where it colonizes the host at the time of weaning and strongly stimulates secretory IgA responses, innate defenses and a potent Th17 response. SFB is a thereby a key member of the microbiota that potently shapes the immunological milieu of the host and influences immune reactivity. In the lab, we are interested in deciphering the novel interaction of SFB with intestinal epithelial cells at the molecular level, how this interaction fosters physiological inflammation in the host, and how the SFB-mediated immune activation results in enhanced resistance to pathogens in and outside of the gut. Aside a better basic understanding of the unique cross talk between this medically-relevant microbe and the host, our long-term goals is to develop a novel vaccine delivery platform against enteropathogens.

Research objectives

We currently focus our investigations of the host-microbiota interaction on the unique cross talk between the commensal SFB and the host. SFB intimately attaches to intestinal epithelial cells, leading to actin recruitment at the site of contact. This interaction is key for the stimulatory potential of SFB and likely involves the conditioning of the immune cells by SFB-mediated stimulation of epithelial cells. For one, we aim to characterize the tight interaction of SFB with the intestinal epithelial cell using a number of proteomic, molecular and immunological approaches. We also aim to better understand how epithelial cells respond to SFB challenge and to identify and characterize host factors involved in the activation of the host immune system. At the same time, we are interested in the molecular mechanisms, and to what extent, SFB can mediate colonization resistance in and outside of the gut. In addition, we aim to establish genetic manipulation techniques for SFB for mutagenesis studies and to express foreign antigens in order to test SFB as a vaccine delivery platform.

2000

Pamela obtained her B.Sc. Honors degree in Biology and Minor in Microbiology from the University of Victoria, British Columbia, Canada in 1998 and her Ph.D. in Microbiology from the University of California at Berkeley in 2005. For her PhD, she investigated the cellular microbiology of the human pathogen Listeria monocytogenes in the laboratory of Professor Dan Portnoy. She then continued in the field of microbial pathogenesis as a postdoctoral fellow with Philippe Sansonetti at the Institut Pasteur in Paris where she explored different aspects of the host-bacterial interaction of the human diarrheal pathogen Shigella flexneri. Pamela then switched to the microbiota field to investigate how commensal bacteria can contribute to the protection of the host from pathogens. For this, she joined Laboratory of Intestinal Immunity of Nadine Cerf-Bensussan the at Institut Imagine in Paris where she worked with the immunostimulatory gut commensal segmented filamentous bacteria (SFB) and was the first to set up an in vitro culturing system, starting the field of cellular microbiology for SFB. Pamela became an INSERM Researcher in 2016 and joined the Necker Institute for Sick Children (INEM) as a group leader in 2018. Her research is supported through national and international funding sources including a prestigious Bill and Melinda Gates Foundation Grand Challenge grant.

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Support(s)

HRH Princess Caroline of Hanover, who through the Princess Grace Foundation, already supports medical research and anything that helps to relieve the sick children in France and around the world, has agreed to commit to our side so that our Center of Molecular medicine continues to meet the current challenges and fight diseases, and in particular the ones affecting children.

Legal mentions

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